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Role of GluN2C‐containing receptors in rodent schizophrenia‐like phenotypes
Author(s) -
Hillman Brandon Geoffrey,
Stairs Dustin,
Dravid Shashank
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1045.5
Subject(s) - ionotropic effect , receptor , schizophrenia (object oriented programming) , glutamate receptor , psychology , potentiator , phencyclidine , nmda receptor , knockout mouse , neuroscience , pharmacology , medicine , biology , psychiatry
There are four classes of ionotropic glutamate receptors classified on the basis of sequence similarity and pharmacology. One class of ionotropic glutamate receptors is the N‐methyl‐D‐aspartate (NMDA) receptor, which is composed of two GluN1 and two GluN2 (A–D) subunits. The physiologic role of GluN2C‐containing receptors has remained poorly understood. We have previously shown that GluN2C knockout mice exhibit deficits in fear acquisition and working memory (Hillman et al., 2011) which mimic the negative symptoms and are consistent with the glutamate hypofunction theory of schizophrenia. To further assess a role of GluN2C in schizophrenia‐like behavior we employed genetic and pharmacologic approaches. We found that GluN2C knockout mice were hypersensitive to phencyclidine‐ and social isolation‐induced hyperlocomotion and these results were further explored using the atypical antipsychotic clozapine and a novel potentiator of GluN2C‐containing receptors (CIQ, Mullasseril et al., 2010). Our results suggest that targeting the GluN2C subunit may have therapeutic relevance in schizophrenia.